Fluorinations ketones

It is more reactive than perchloryl fluoride and therefore not without danger. It forms, for instance, a highly explosive product with pyridine. Like perchloryl fluoride it reacts with enol ethers, esters and enamines, but at lower temperature (—78°) to yield the fluorinated ketones as well as addition... 

Preparation of Tnfluoromethyl Ketones and Related Fluorinated Ketones Begue, J P, Bonnet-Dalpon, D Tetrahedron 47. 3207-3258 245 ... 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

Similarly, fluorinated ketones are prepared and react with enamines [50], This reaction involves the intermediacy of an a,P-ethylenic ketone and leads to annelation-aromatization products [5tJ] (Table 13) (equation 37). 

Another reaction that has potential is the intramolecular ene reaction, which preferentially results in five-membered rings Because fluorinated ketones have a propensity for undergoing intermolecular ene reactions [5S], this reaction has tremendous synthetic possibilities Only one example of an ene reaction of an unsaturated trifluoromethyl ketone has been reported, but it indicates the potential of the methodology [59] (equation 59)... 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

Enamines from steroidal ketones have been fluorinated by means of perchloryl fluoride (119,120) to give the a-fluorinated ketones. Theenamino ketone (49) was brominated to give a salt from which the bromoenamino ketone (175) was isolated on treatment with dilute carbonate solution (121). 

Kilbardin, A.M., Gazizov, T.K., and Pudovik, A.N., Reactions of diethyl tri-methylsilyl phosphite and of acetyl diethyl phosphite with fluorinated ketones,. Gen. Chem. U.S.S.R., 45,1947,1975. 

Trifluoromethyl)trimethylsilane has been prepared by a modification5 of the procedure originally published by Ruppert.4 The optimized yield is 75%. Other less convenient methods are also available for its preparation. (Trifluoromethyl)trimethylsilane acts as an in situ trifluoromethide equivalent under nucleophilic initiation and reacts with a variety of electrophilic functional groups. Carbonyl compounds such as aldehydes, ketones and lactones react rather readily5 7 with (trifluoromethyl)trimethylsilane under fluoride initiation. The reagent also reacts with oxalic esters,8 sulfonyl fluorides,9 a-keto esters,10 fluorinated ketones,11 and... 

Scheme 2.16. Preparation of fluorinated ketones by way of fluorinated alkenylcopper species.

A series of fluorinated biaryl ketones (13) was reported by Denmark and coworkers in 1999 and 2002 (Fig. 4) [22, 40]. The introduction of fluorine atoms at the a-position of the reacting carbonyl increased the efficiency of the epoxidation. Fluorinated ketones 13b and 13c displayed high reactivity and good enantioselectivity... 

In 1998, Armstrong and coworkers reported tropinone-based fluorinated ketone 23a to give good enantioselectivities for several fran -olefms (Fig. 7) (Table 2, entries 1, 6) [48, 49]. The replacement of the fluorine atom with an acetate group... 

Di- and trifluoromethylketones inhibit a great number of esterases and proteases with often very high inhibition constants. Although the fluorinated ketone... 

Di- and trifluoromethyl ketones inhibit a great number of esterases and proteases with often very high inhibition constants (cf. Chapter 7). Although the fluorinated ketone is covalently bonded to the nucleophilic residue of the enzyme, the inhibition is reversible, as the inhibitor could be displaced by another nucleophile. The covalent nature of the interactions as well as the tetrahedral structure of the adducts have been demonstrated by kinetic studies, by NMR experiments, and by the X-ray diffraction of the enzyme-substrate complexes. ... 

Figure 3.24 Fluorinated ketones, transition state analogue inhibitor of chymotrypsin. ...

The gallium(lll) triflate-mediated condensation of anthranilic acid with fluorinated ketones gave the corresponding 2,2-disubstituted l,2-dihydro-4//-3,l-benzoxazin-4-ones in high yields <20070L179>. 

Table 1. Baker s Yeast Reduction of Fluorinated Ketones ...

For a review of addition to fluorinated ketones, see Gambaryan Rokhlin Zeifman Ching-Yun Knunyants Angew. Chem. lnt. Ed. Engl 1966, J, 947-956 Angew. Chem. 78, 1008-1017). 

Table 10. Toxic Data of Fluorinated Ketones and Oxiranes...

In contrast, the partially fluorinated ketone 3,3,4,4,5,5,5-heptafluoropentan-2-one is only partially degraded87 by cobalt(III) fluoride at 80 C it gives mainly perfluorobutanoyl fluoride. 

While there are no examples of the formation of fluorinated unsaturated aldehydes by de-halogenation, dehalogenation is the preferred method for the synthesis of reactive fluorinated ketenes. Examples of dehalogenations giving unsaturated fluorinated ketones and fluorinated ketenes are listed in Table 9. 

Table 9. Formation of Unsaturaled Fluorinated Ketones, and Fluorinated Ketenes. by Dehalogenation...

The synthesis of fluorinated butoxides was carried out by interaction of metal hydrides with corresponding alcohols in ether media [467, 947]. The interaction of fluorinated ketones with sodium in THF or aqueous alkali led to the derivatives of perfluoropinacol ... 

The first attempts to prepare cobalt and nickel ethoxides were reported in 1936 by Meerwein [1102] and Kandelaki [875]. Application ofNaOR in the exchange reactions could not, however lead to the obtaining of the pure products of purpose as they were insoluble in the parent alcohol. Application of LiOR for this purpose permitted Adams et al. in 1966 to obtain the individual M(OMe)2 — derivatives of id-transition elements in the series from Cr to Cu [6]. In the 1980s Mehrotra et al. have described the homologous series of Ni(OR)2 — from methoxide to r-hexyloxide [99], and also Co(OR)2, where R = Me,Et, Pr [1108]. On the alkoxylation of CoH(N2)(PPh3)3 by esters, phenol, or fluorinated ketones, Hayashi et al. [720] have obtained a series of tetrahedral [Co (OR)(PPh3)3] complexes. 

Equilibrium constants for hydration and hemiacetal fonnation have been calculated for representative highly fluorinated ketones.5 Both reactions were substantially more favourable in cyclic than acyclic systems. 

Hydration of highly fluorinated ketones has been referred to under Acetals above.5 2-Acetyl-l-methylpyridinium ion is 8% hydrated in water see Enolization below. 

Enhancement of P by an inductive contribution can also be seen in fluorinated ketones. For example, 4-methoxyben-zaldehye has a P of 2.2 x 10 30 esu and 1 of 3.5 Debye while the trifluoromethyl ketone compound (21) as the ac-... 

It should be noted that the related imine-oxaziridine couple E-F finds application in asymmetric sulfoxidation, which is discussed in Section 10.3. Similarly, chiral oxoammonium ions G enable catalytic stereoselective oxidation of alcohols and thus, e.g., kinetic resolution of racemates. Processes of this type are discussed in Section 10.4. Whereas perhydrates, e.g. of fluorinated ketones, have several applications in oxidation catalysis [5], e.g. for the preparation of epoxides from olefins, it seems that no application of chiral perhydrates in asymmetric synthesis has yet been found. Metal-free oxidation catalysis - achiral or chiral - has, nevertheless, become a very potent method in organic synthesis, and the field is developing rapidly [6]. 

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